A new model of genetic hypertension has been produced by inserting the gene for mouse submandibular renin (mRen-2) into the rat genome. The resulting transgenic rat (TG) shows increased expression of the renin- angiotensin cascade (RAS) in the brain, adrenal and blood vessels. Since the pharmacological blockade of the RAS system reduces the hypertension in these rats, this model provides an excellent means for determining the role of tissue angiotensin expression in physiological processes. Research has indicated that central angiotensin peptides and osmotic stimuli activate vasopressin pathways to produce a coordinated cardiovascular and endocrine response. Preliminary data shows that there are increases in the levels of brain angiotensin and brainstem vasopressin in the TG rat, coupled with changes in the vasopressin response to central angiotensin. IT is hypothesized that the increased brain angiotensin expression elicits changes in the vasopressin axis and the consequent cardiovascular abnormalities. Thus, the focus of the proposal is on central nervous system angiotensin-vasopressin interactions in the TG and control, TG-negative rat. The research program includes studies of cardiovascular and vasopressin responses to central application of angiotensin peptides and osmotic stimuli using in vivo microdialysis of nuclear, brainstem and blood. This will be coupled with the evaluation of the angiotensin receptor subtypes which mediate these responses and the role of central versus peripheral vasopressin receptors. Enzyme inhibitors will be used to test the vasopressin in the cardiovascular changes, excitotoxin PVN lesions will be used to produce a depletion of brainstem vasopressin. Finally, alterations in central vasopressin neurons will be examined utilizing in situ hybridization for peptide mRNA expression under basal and stimulated conditions.